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犬乳腺肿瘤的分子与病理生物学:为人类乳腺癌建立转化模型。

Molecular and Pathobiology of Canine Mammary Tumour: Defining a Translational Model for Human Breast Cancer.

机构信息

Department of Animal Science, Federal University of Ceará, Fortaleza, Brazil.

Graduate Studies Program in Biotechnology, University of Vale do Taquari-Univates, Lajeado, Brazil.

出版信息

Vet Comp Oncol. 2024 Sep;22(3):340-358. doi: 10.1111/vco.12996. Epub 2024 Jul 16.

DOI:10.1111/vco.12996
PMID:39011576
Abstract

Canine mammary tumours (CMT) have histological, clinicopathological and molecular resemblances to human breast cancer (HBC), positioning them as viable models for studying the human disease. CMT initiation and progression occur spontaneously in immune-competent animals, which challenge the suggested limitations of genetically modified mice, also enabling the evaluation of immunotherapies in canine patients. Dogs have shorter life expectancy compared to humans, and cancer advances more rapidly in this species. This makes it possible to perform studies about the clinical efficacy of new therapeutic modalities in a much shorter time than in human patients. The identification of biomarkers for tumour subtypes, progression and treatment response paves the way for the development of novel therapeutic and diagnostic approaches. This review addresses the similarities between CMT and HBC and the molecular signatures identified in CMT samples that have been explored to date. We proposed a detailed molecular exploration of the CMT stroma using state-of-the-art methods in transcriptomics and proteomics. Using CMT as an analog for HBC not only helps to understand the complexities of the disease, but also to advance comparative oncology to the next level to prove the claim of dogs as a valid translational model.

摘要

犬乳腺肿瘤(CMT)在组织学、临床病理学和分子水平上与人乳腺癌(HBC)相似,使它们成为研究人类疾病的可行模型。CMT 的发生和发展在免疫功能正常的动物中自发发生,这挑战了对基因修饰小鼠的建议限制,也使犬科患者的免疫疗法评估成为可能。与人类相比,狗的预期寿命更短,而且这种物种的癌症进展更快。这使得有可能在比人类患者短得多的时间内研究新治疗方法的临床疗效。肿瘤亚型、进展和治疗反应生物标志物的鉴定为开发新的治疗和诊断方法铺平了道路。这篇综述讨论了 CMT 和 HBC 之间的相似性,以及迄今为止在 CMT 样本中鉴定出的分子特征。我们建议使用转录组学和蛋白质组学的最新方法对 CMT 基质进行详细的分子探索。将 CMT 作为 HBC 的模拟物不仅有助于理解疾病的复杂性,还有助于推进比较肿瘤学的下一阶段,以证明狗作为有效转化模型的说法。

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A Small-Molecule Compound Targeting Canine Mammary Cancer Regulates CXCL10 and MECOM Transcripts via Histone Modifications in CMT-N7.一种靶向犬乳腺癌的小分子化合物通过CMT-N7中的组蛋白修饰调节CXCL10和MECOM转录本。
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Canine, Feline, and Murine Mammary Tumors as a Model for Translational Research in Breast Cancer.
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